The group of organisms known as the mutans streptococci possess the ability to metabolize a variety of sugars, resulting in acid and extracellular glucan production, both of which contribute to the development of human dental caries. The overall goals of this study are to understand the genetics of sugar metabolism and further characterize at the molecular level the various factors involved in the virulence of this organism. To achieve this goal this proposal will focus on two main areas of investigation; first, those factors involved in the production and regulation of extracellular proteins which synthesize and associate with glucans; and second, a further definition of the pathways of intracellular sugar metabolism. The specific aims of this proposal are to: 1 Define in further detail the manner in which extracellular proteins are involved with glucan production and association. 2. Characterize the manner in which extracellular proteins are subjected to regulation. 3. Elucidate the pathways of sugar metabolism encoded in the clustered gene region responsible for glucose, galactose, and multiple sugar metabolism. 4. Identify and characterize the regulatory mechanisms involved in intracellular sugar metabolism. The results from this study should provide important information at the molecular level for the elucidation of the genetics of sugar metabolism in the mutans streptococci. Knowledge of the structure and function of various components involved in sugar metabolism, as well as the mechanisms involved in their control and regulation, should provide meaningful insight into how these organisms are able to function and initiate caries. Such information is essential for the formulation of the strategies to disrupt these mechanisms and the design of rational approaches to control caries.